This invention relates to aminocrotonyl derivatives of 4-nitropyridine N-oxides used as sensitizers of tumor cells to therapeutic radiation. It also relates to the process of preparing such compounds starting with 4-nitro-3-fluoropyridine N-oxide and reacting it with amino substituted crotonate ester. In addition, the present invention relates to pharmaceutical compositions comprising such aminocrotonyl pyridine N-oxides and to methods of treatment comprising administering such compounds to patients undergoing radiation treatment to enhance the effectiveness of such treatment.
At the present time, certain other unrelated compounds are in experimental clinical use as radiation sensitizers. However, these compounds--for example, metronidazole and misonidazole--suffer from the drawback that they also cause neurotoxicity which limits their usefulness. The compounds of the present invention are effective radiation sensitizers, but are believed to have a more favorable therapeutic ratio.